Over the last years, various approaches have been proposed to improve the delivery of drugs at the target site. Firstly, the drug must be administered by a suitable and easy route, such as via oral or rectal routes, and secondly the active ingredient must be delivered at the target cells in an active form. Some drugs, in particular proteins and peptides, are poorly absorbed and unstable during passage through the gastrointestinal tract (GIT). Many attempts have been made so far to improve delivery, in particular via the oral route, of polypeptides and peptides, such as for instance insulin (for treating diabetes), interferons (for treating hepatitis), cytokines (for treating cancers), etc. However, today the administration of these drugs is via parenteral injection. Today, 40% of the new drugs can only be administered through parenteral injection.
Despite the inherent problems faced when attempting to administer proteins and peptides orally, various approaches have been proposed to improve oral absorption. Plausible strategies have included chemical modification to stabilise the drug and/or to render it more lipid-soluble and hence improve its chances to diffuse across the lipid membrane or the GIT. Other researchers have added stabilising agents such as peptidase inhibitors (e.g. aprotinin) to reduce metabolic loss, while others have used various absorption promoting agents in the form of non-ionic surface active agents, bile salts and analogues thereof, phospholipids, chelating agents or acyl carnitine. Numerous patents and publications describe also methods for encapsulating active ingredients into nano- or micro-particles. But, so far, none of the developed delivery systems is totally satisfactory, particularly for insulin. For instance, the delivery systems disclosed so far have permitted an insulin absorption of 2-5% only.
Subjects suffering from diabetes type 1 or 2 are often treated with insulin. While the injection devices are improving and are less invasive (e.g. pen-like devices), injections still present disadvantages and remain very unpopular. Non-injectable formulations will present great advantages. In addition to being more patient-friendly, such formulations could improve compliance, leading to better treatment and a reduction in diabetes-related complications.
The inventors have previously uncovered that stirring two types of lipids with some metallic salts allowed to increase metal bioavailability and consequently to obtain same therapeutic activity with 1000 to 5000 lower doses; the potential toxicity of the said metal salts could then be reduced [see U.S. Pat. No. 6,129,924, WO 02/36134 and WO 2004/075990, for examples].
It is an object of the present invention to overcome disadvantages of the prior art. More particularly, it is an object of the invention to provide a drug delivery system comprising an active ingredient, which can be administered orally and give a satisfactory drug bioavailability.